1. Field of the Invention
The present invention relates to functional domains and fragments of the intercellular adhesion molecule, ICAM-1. Such functional domains and fragments may be used in the treatment of viral, and particularly rhinoviral disease.
2. Description of the Related Art
I. The Intercellular Adhesion Molecule ICAM-1 and Cellular Adhesion
The intercellular adhesion molecule ICAM-1 was first identified and partially characterized according to the procedure of Rothlein, R. et al. (J. Immunol. 137:1270-1274 (1986)), which reference is herein incorporated by reference. ICAM-1, its preparation, purification, and characteristics are disclosed in U.S. patent application Ser. Nos. 07/045,963 (filed on May 4, 1987), 07/115,798 (filed on Nov. 2, 1987), 07/155,943 (filed on Feb. 16, 1988), 07/189,815 (filed on May 3, 1988) and 07/250,446 (filed on Sep. 28, 1988), all of which applications are herein incorporated by reference in their entirety.
ICAM-1 was initially realized as being involved in the process of cellular adhesion between endothelial cells and leukocytes. Cellular adhesion is the process through which leukocytes attach to cellular substrates, such as endothelial cells, in order to migrate from circulation to sites of ongoing inflammation, and properly defend the host against foreign invaders such as bacteria or viruses. An excellent review of the defense system is provided by Eisen, H. W., (In: Microbiology, 3rd Ed., Harper and Row, Philadelphia, Pa. (1980), pp. 290-295 and 381-418).
One of the molecules on the surface of endothelial cells which participates in the adhesion process is ICAM-1. This molecule has been shown to mediate adhesion by binding to molecules of the CO-18 family of glycoproteins which are present on the cell surfaces of leukocytes (Sanchez-Madrid, F. et al., J. Exper. Med. 158:1785-1803 (1983); Keizer, G. D. et al., Eur. J. Immunol. 15:1142-1147 (1985)). This glycoprotein family is composed of heterodimers having one alpha chain and one beta chain. Although the alpha chain of each of the antigens differed from one another, the beta chain was found to be highly conserved (Sanchez-Madrid, F. et al., J. Exper. Med. 158:1785-1803 (1983)). The beta chain of the glycoprotein family (sometimes referred to as xe2x80x9cCD18xe2x80x9d) was found to have a molecular weight of 95 kd whereas the alpha chains were found to vary from 150 kd to 180 kd (Springer, T., Fed. Proc. 44:2660-2663 (1985)). Although the alpha subunits of the membrane proteins do not share the extensive homology shared by the beta subunits, close analysis of the alpha subunits of the glycoproteins has revealed that there are substantial similarities between them. There are three major members of the CD-18 family: p150,95, MAC-1 and LFA-1. Mac-1 is a heterodimer found on macrophages, granulocytes and large granular lymphocytes. LFA-1 is a heterodimer found on most lymphocytes (Springer, T. A., et al. Immunol. Rev. 68:111-135 (1982)). P150,95 has a tissue distribution similar to Mac-1, and also plays a role in cellular adhesion (Keizer, G. et al., Eur. J. Immunol. 15:1142-1147 (1985)). Reviews of the similarities between the alpha and beta subunits of the LFA-1 related glycoproteins are provided by Sanchez-Madrid, F. et al., (J. Exper. Med. 158:586-602 (1983); J. Exper. Med. 158:1785-1803 (1983)).
II. The Cellular Receptor for Human Rhinovirus
Abraham et al. (J. Virol. 51:340-345 (1984)) discovered that the majority of randomly selected human rhinovirus (xe2x80x9cHRVxe2x80x9d) serotypes were able to bind to the same cellular receptor. A monoclonal antibody was subsequently developed by Colonno et al. (Colonno et al., J. Cell. Biochem. Suppl. 10 (part D):266 (1986); Colonno et al., J. Virol. 57:7-12 (1986); Colonno et al., European Patent Application Publication No. 169,146) which was capable of blocking attachment of HRV of the major serotype to the surfaces of endothelial cells. The endothelial cell receptor protein recognized by this antibody was isolated and found to be a 90 kd protein (Tomassini et al., J. Virol. 58:290-295 (1986).
The present invention relates to the use of functional derivatives of Intercellular Adhesion Molecule-1 (ICAM-1) in anti-viral therapy. Of particular concern to the invention are those functional derivatives of ICAM-1 which comprises fragments of the intact ICAM-1 molecule.
In detail, the invention provides a method for treating viral infection in an individual in need of such treatment, wherein the method comprises providing to the individual an amount of a fragment of ICAM-1 or a fragment of a functional derivative of ICAM-1 sufficient to suppress viral infection.
The invention further provides a method of diagnosing the presence of viral infection, the method comprising:
(a) incubating a biological sample suspected of containing a virus with a detectably labeled ICAM-1 functional derivative;
(b) determining whether any of the detectably labeled ICAM-1 functional derivative has become bound to virus.
The invention further provides a method of preventing viral infection which comprises providing to a recipient a vaccine composition, the composition containing a virus bound to a functional derivative of ICAM-1.